Figure 1

Assessing ED effects on imprint reprogramming in the mouse germline. (Top) Reprogramming in the mouse germline. Exposure of pregnant mice to EDs may directly affect the G0 dam and the G1 soma and G1 germline, and indirectly, the G2 soma that develops from G1 germ cells. DNA methylation patterns are globally remodeled during gametogenesis in both male (above) and female (below) embryos/fetuses in the chromosomes that are paternally (blue) or maternally (red) inherited. The 5-methylcytosine levels (blue and pink curves) are globally reduced in the primordial germ cells (PGC) of both sexes; DNA methylation of imprinted DMRs is similarly erased (brown horizontal arrow) by mid-gestation (13.5 dpc). In the male germ cells, global DNA methylation is largely reset and paternal imprints are newly established (blue arrow) in prospermatogonia prior to birth and maintained (black horizontal arrows) into spermatozoa (SPZ). In female germ cells, global DNA methylation and maternal imprints are established (red arrow) after birth during oocyte (OO) growth (from 5 to 20 dpp). The imprinting marks are maintained (black arrows) through global remodeling at fertilization and embryo development. (Bottom) Daily gavage was given to pregnant dams in the time windows of ‘Exposure A’ or ‘Exposure B’ to affect the erasure phase of the germline reprogramming in PGCs or the establishment phase in MGC. The timeline (not to scale) is marked with gestational age (dpc) on top, and also with the age after birth (dpp) at the bottom. In our related publication [32], maintenance of imprinting was analyzed in the exposed G1 soma after ‘Exposure A’. In the current study, we focused on the effect of EDs on imprinting via the exposed G1 germ cells. Experimental endpoints are indicated by the arrows pointing down.